The Human Genome Oracle by National Human Genome Center at Howard University

December 2015

THE HUMAN GENOME

ORACLE

The Voice of the Living Genome, where knowledge is power, but wisdom is supreme

The 2nd Decade

NHGC NexGen Genomics

Human Genome Big Data: Through the Lens of a Theoretical Physicist

Advances in Genomic Information Research on DNA Sequence Variation

L A R U G E U A SU N I IS

2015 The International Year of Light and Light Technologies

THE COMING OF THE HUMAN GENOME ORACLE The Voice of the living genome, with knowledge as power, but wisdom is supreme

NOME ST E G E OR TH Y

Human origins, migrations, adaptations, transformation and liberation, now revealed in DNA sequence variation. y. D iv nit i v ersit i y is the hallmark of d

INAUGURAL ISSUE Truth is the ultimate theoretical construct for all science. - Georgia M. Dunston, PhD

Content 06

The Global Genome Generation Great Commission (TGGGGC) Georgia M. Dunston

From the Founding Director Georgia M. Dunston

National Human Genome Center Timeline of First Decade

Human Genome Big Data: Through the Lens of A Theoretical Physicist James Lindesay

Howard University Louis Stokes Health Sciences Library About the library

Advances in Genomic Information Research on DNA Sequence Variation About the NHGC Postdoctoral Scholars

What Attracted Me to the National Human Genome Center at Howard University? The NHGC Team

Howard University Interdisciplinary Research Building About the research building

The “Soul’” Determinant of Health and Disease Georgia M. Dunston and Philip Kurian

“Truth Is...” Crossword Puzzle Niya McKie

THE HUMAN GENOME

ORACLE Oracle: (noun) In mathematics and computer science, an oracle is a black-box entity, with mysterious or unknown inner workings, that is capable of solving decision problems of any complexity class, even those that are traditionally uncomputable or undecidable.

Howard University President Wayne A.I. Frederick, MD, MBA, FACS Dean, HU College of Medicine Hugh E. Mighty, MD, MBA, FACOG Contributing Writers Muneer Abbas, PhD Daniel Achinko, PhD Victor Apprey, PhD Georgia Dunston, PhD Latifa Jackson, PhD Philip Kurian, PhD James Lindesay, PhD Ashelyn Mack Tshela Mason Niya McKie Address National Human Genome Center Howard University 2041 Georgia Avenue, NW Cancer Center Building Sixth Floor, Suite 615 Washington, DC 20060

The Global Genome Generation Great Commission (TGGGGC) For unto us, this generation of health scientists, the whole human genome sequence is given. Unto us, the knowledge of Life encoded in the human genome is revealed. And the science, technology, engineering, and mathematics (STEM) of eLife at the genome level is established upon the biophysics of DNA sequence variation, expressed in population diversity and human identity.

Telephone 202.806.9436 Fax 202.986.3972 Homepage www.genomecenter.howard.edu Acknowledgements The Human Genome (HG) Oracle is a research education, communication, and promotion publication of the National Human Genome Center (NHGC) at Howard University, launched in December 2015 with this inaugural issue. The HG Oracle is a product of the visionary leadership of the NHGC founding director, Georgia M. Dunston, PhD, and is produced under the NHGC logo. All rights are reserved. Reproduction in whole or part without permission is prohibited. Printing and distribution costs for the HG ORACLE are paid for by contributions to the Howard University College of Medicine NHGC-designated fund account.

Giving voice to the living genome, the Human Genome Oracle is dedicated to communicating genomic information on the science of Life encoded in the human genome and expressed hierarchically in living systems, at all levels of biological organization.

FROM THE FOUNDING DIRECTOR Georgia M. Dunston

As the founding director of the National Human Genome Center (NHGC) at Howard University, my heart is joyful and my mind reflective in this season of the year, as we launch the December 2015 Inaugural Edition of the Human Genome Oracle, a benchmark for the second decade of the NHGC. Giving voice to the living genome, the Human Genome Oracle is dedicated to communicating genomic information on the science of Life encoded in the human genome and expressed hierarchically in living systems, at all levels of biological organization. For with completion of the Human Genome Project (HGP) came a new knowledge base for the science of biology; knowledge as old as the origins of humanity itself, yet as new as the most recent genome discovery. Timeless knowledge, whose time has come. While the first decade of the NHGC pivoted on the inclusion of African Americans and populations of African descent in the mainstream of the HGP, the second decade builds upon and extends knowledge gained from research on human genome variation. Moreover, the first decade of the HGP set the stage for the formation of the NHGC in engaging Africa and African populations in the International Haplotype Map (HapMap) Project, an unprecedented resource on common patterns of genome variation used worldwide by researchers to map genes affecting health, disease, and responses to drugs and environmental factors. The second decade of the HGP finds NHGC investigators actively drilling down through population differences in common patterns of genome variation to uncover “new life” embedded in the substructure of DNA sequence variation. The advent of genome-wide variation resources like the HapMap opened a new era in population genetics, offering an unprecedented opportunity to investigate evolutionary forces that have shaped genome variation in natural populations. Indeed, a milestone of the second decade of the NHGC has been the emergence of the collaborative biophysics research and interdisciplinary development group (BRIDG), with its focus on the biophysical characterization of the human genome as the most sophisticated living information and communication system known to humankind.

Genomes are emergent living information systems.

The BRIDG approach to the science of the human genome is both transformative and novel in exploring functional aspects of common variation and population genetics from first principles of thermodynamics and statistical physics. In so doing, the BRIDG introduced the term genodynamics to describe this new biophysical perspective on common genome variation, in which genomic information is structured in patterns of common variants, like single nucleotide polymorphisms (SNPs). The seminal BRIDG publication in 2012 entitled “A new biophysical metric for interrogating the information content in human genome sequence variation: “Proof of concept” signaled the beginning of the NHGC second decade, with the 2015 inaugural edition of the Human Genome Oracle serving as a middecade highlight. With a focus on decoding genomic information, NHGC investigators use human genome sequence variation for gene and self discovery, in pursuing the Center’s mission to explore the science and teach the knowledge of DNA sequence variation and its interaction with the environment in the causality, treatment, and prevention of diseases common in populations of African ancestry. With 2015 declared as the International Year of Light and Light Technologies, it is fortuitous that the Human Genome Oracle is launched at this time in human history and in this season of the calendar year. As the third-millennium foundation of knowledge on the science of Life communicated in and through the living genome, the Human Genome Oracle gives voice to life principles (i.e., truths) incarnated in human identity and inheritance. Articles in the Human Genome Oracle are dedicated to telling the human genome story of human origins, migrations, adaptations, transformations, and liberations, encoded in the human genome and expressed in the science of biology. We submit that the human genome story is an African story of life eternal (i.e., eLife), one that continues from generation to generation at Howard University, now interfacing advances in the forefront of genomics with theoretical physics at the frontier of the life sciences. It is my hope as founding director of the NHGC that readers of the Human Genome Oracle will be informed and inspired by words of wisdom on the science of biology and identity encoded in the human genome and expressed in articles contributed by the writers. I wish all an exceedingly abundant and fulfilled life. In Peace & Truth, Georgia M. Dunston

Sharing the ViSion for Th e Nat iona l Hu m a n G e n o m e C e n t e r NHGC the 1st Decade

Howard University

2001

Landmark Publications on complete working draft of human genome sequence

Formal Announcement and Dedication of NHGC International Haplotype Map

2002 Project Launched NHGC GRAD Project Workshop I

2003

Finished human genome sequence

NHGC Meeting on Human Genome Sequence Variation and “Race”: The State of the Science

2004

2005 Nature publishes human genome haplotype map

Publication of Nature Genetics Supplement on Genetics for the Human “Race” based on NHGC 2003 meeting

Year of Physics 100th Anniversary of Einstein’s E=mc2

s we map the human genome, unfold the particularities of life itself, and begin to understand the very mechanisms that produce life, I want the investigations of our scientists and students to be informed by values, by the ancient truths, by a sense not of the simple randomness of life, but of its order1...revealed in the human genome sequence. H. Patrick Swygert Former President of Howard University

Excerpt from 1998 message at Rankin Chapel

SNP haplotype variation, complex

2006 diseases & health disparities

2007

HBCU National Research Conference

Zeta Phi Beta Human Genome Conference

2008 NIH Cancer Health Disparities Congressional Black Caucus Health Braintrust

2009

1000 Genomes Project

Inauguration of President Barack Obama

2010

Healthy People 2010

Human Genome Big Data: Through the Lens of A Theoretical Physicist James Lindesay, PhD

James Lindesay, PhD, is Professor and founding director of the Computational Physics Laboratory in the Department of Physics and Astronomy in the College of Arts and Sciences at Howard University. He has been visiting professor at Hampton University, Stanford University, and a visiting faculty scientist at the Massachusetts Institute of Technology (MIT). Achieving his SB degree in Physics from MIT, with the MS and PhD degree in Physics (Theoretical Physics) from Stanford University, his research fields are Astrophysics, Cosmology, Particle and Nuclear Physics, Condensed Matter Physics, Biophysics, and Computational Physics. He is the author of a book on Foundations of Quantum Gravity published in 2013 by Cambridge University Press, which examines the foundational consistency of quantum mechanics incorporated within relativistic frameworks and explores how the subtleties of quantum coherence can be consistently incorporated into Einstein’s theory of gravitation.

The human genome is a dynamic information and communication system with a storage content comparable to that of a couple of DVD’s. The various expressions of this magnificent system of biochemical bits result in all past, present, and future human beings, along with their co-creative efforts. The genome (as well as life itself) is an emergent phase transition in the dynamics of the universe, demonstrating creativity within a framework of rules for sharing and interacting. Furthermore, biologically coherent “haplotypes” emerge as fundamental units within the genome due to its interaction with a specific environment. The use of such markers has become popular in determining the ancestral pathways leading to present-day individuals and groups. As humans have migrated throughout our history, we have settled in various environments that exhibit some favorable characteristics and pose new challenges and stressors. As human populations have settled into these environments, the human genome has adapted the distribution of its expressions in a manner that optimizes its survivability and flourishes within each of these environments, maintaining continuity under unforeseen influences. By examining the information dynamics among differing human populations, one can gain insights into how the varying environmental stimuli and stressors directly influence those dynamic elements of the genome that make us individuals. The same information dynamics that drive the creation of galactic clusters, galaxies, suns, and planets in our cosmology also drive the wonderful variation in the human genome expressed through ourselves and our living collaborators. The human genome continually reexpresses itself by finding a subtle balance of variation (or differences) with conservation (or preservation of important characteristics and traits). With my colleagues in the National Human Genome Center and the Computational Physics Lab here at Howard, we are developing equations that model the cosmically driven diversity of humanity exemplified around us today, finding collective expressions of genomic energies that

mold our adaptation to the multitude of environments that can support life. “Genodynamics” provides us with a science that formulates whole genome response to environmental stimuli, offering useful tools for understanding population diversity as well as individual responses to stressors. For instance, we have found that sociologically defined concepts such as race can no longer be meaningfully used as a discriminator that separates humanity. Humanity is defined by the expression of its genome, and all within it that can co-regenerate its populations. The common concept of “race” is the human genome’s response to optimize a population’s survivability under sustained and unpredictable celestial and geographic influences. Culture arises as collective social mores develop within a surviving, diverse population under the stresses and benefits of its homeland. As it turns out, the human genome is an interface between the known, knowable, and unknowable aspects of the science of life. Surprisingly, we discovered that some aspects of the recombination of palindromic sequences in the genome involve quantum coherence, embodying unknowable “choice” (through quantum entanglement). Although most aspects of the copying of the genome involve straightforward classical transcription (like copying a DVD), some aspects of living expression have characteristics that cannot be completely determined through an equation. Any aspects of genomic expression and re-expression that are not deterministic demonstrate that the genome’s programming is not purely robotic. Our present efforts involve constructing information maps that describe the “geno-scape” of dynamic genomic sites. These maps exhibit hills and valleys that parameterize how favorable various genomic regions are under the multitude of influences upon populations and individuals in given environments. Maintained valleys are very favorable combinations of variants for sustaining humanity. The hills are maintained variants

needed for response to unforeseen events, diseases, adaptability, immune response, etc. The correlations of those influences that can be mathematically quantified, with genomic sites and regions that have known biology, provide a means of determining whole genome response to such influences. This affords the scientific community new tools for understanding and treating environmentally provoked diseases (like asthma, skin cancer, malaria, etc.), as well as tools for developing human-produced influences (such as drugs, therapies, etc.) and determining their effects upon individuals. Comparisons between various geno-scapes exhibit those â&#x20AC;&#x153;adaptive forcesâ&#x20AC;? that manifest as changes in the heights of hills and depths of valleys on the dynamic information maps. The sheer magnitude of the amount of information that needs to be characterized and categorized keeps our team quite busy, and we have just begun to scratch the surface of utility of our formulations. However, we are excited about the successes so far attained, as well as those prospects that continue to be uncovered as we proceed. I end by noting that our interdisciplinary collaboration (BRIDG) has certainly proven to be quite satisfying, as we each continue in our quests for personal and professional fulfillment. I urge anyone willing to stretch their horizons to put forth the initial effort to establish a common language with a willing colleague whose expertise lies in a field outside of your comfort zone. The rewards are unpredictable, and can be deeply gratifying.

As it turns out, the human genome is an interface between the known, knowable, and unknowable aspects of the science of life.

The building in 2001 of the Louis Stokes Health Sciences Library, a brick-and-mortar repository of human history, is synchronous with publication also in 2001 of the first complete draft of the human genome, a living repository of human history. To these repositories of human history is added the dedication of the National Human Genome Center at Howard University, commissioned also in 2001, to go and tell to all nations and peoples the whole genome story of eLife, encoded in DNA sequence variation, and expressed collectively in population diversity, personalized in human identity. -Georgia M. Dunston, PhD NHGC founding director

Louis Stokes Health Sciences Library - Built in 2001, the Louis Stokes Health Sciences Library (LSHSL) provides health information resources to the international health sciences community to support the local and global elimination of health disparities.Â The LSHSL is a symbol of knowledge, learning, practice and research, with a service focus on excellence in teaching, lifelong learning, research and health sciences resources for Howard University Health Sciences students, faculty, staff and the community. 13

Advances in Genomic Information Research on DNA Sequence Variation NHGC Postdoctoral Scholars, Philip Kurian and Latifa Jackson

Philip Kurian, PhD, was born in Charleston, SC, and received his Bachelor’s degrees in Physics and Public Policy from Duke University, MSEd degree in Urban Education from the University of Pennsylvania, and PhD degree in Physics from Howard University in 2013. He is building a research program around how coherent energy transport in DNA affects macroscopic genomic functions and is developing new research collaborations connecting his findings to studies of chronic degenerative illnesses, such as Alzheimer’s disease, cancer, and HIV/AIDS. Since beginning his postdoctoral work at the NHGC, he has been invited to present his work in Italy, Finland, and Nigeria, in addition to other local academic institutions.

Latifa Jackson, PhD, received Bachelor’s degrees in Cell/Molecular Biology and Genetics, BS, and French Language and Literature, BA, from the University of Maryland at College Park and Master’s degree in Ecology & Evolutionary Biology from the University of Arizona. In 2014, she completed the PhD in Biomedical Science in the School of Biomedical Engineering, Science and Health Systems at Drexel University. Her career goal is to build models of human immunological responses to key infectious diseases that account for how genetic variants and environmental factors contribute to disease phenotypes.

Quantum Visions of Genomic Science: An interview with the first NHGC-BRIDG Postdoctoral Scholar, Philip Kurian, PhD Why did you come to the National Human Genome Center (NHGC)? The National Human Genome Center has been an answered prayer. I was led to the NHGC in 2009 while a graduate student in the Department of Physics and Astronomy at Howard University. Meeting the founding director was a transformative experience, as I saw in her the realization of what I wanted to combine my passion to know with my dedication to serve. Indeed, the NHGC is a shining watchtower at Howard, exemplifying the institution’s motto Veritas et Utilitas (Truth and Service). The Center’s mission “to explore the science of and teach the knowledge about DNA sequence variation and its interaction with the environment in the causality, prevention, and treatment of diseases common in African American and other African Diaspora populations” represents the union of puzzle pieces in the kaleidoscope of my life pursuits. As my dissertation1 advisor, Professor Georgia Dunston encouraged the conceptualization of research questions motivated from my personal interests in the physics of living systems. Since the NHGC’s inception in 2001, her vision as founding director has included studying DNA sequence variation at the quantum level. Pursuing this research direction in collaboration with Professor James Lindesay, a theoretical physicist in the Computational Physics Laboratory at Howard, has been both exhilarating and demanding. However, through painstaking toil punctuated by the joys of discovery, our efforts are slowly beginning to bear fruit.2 In this regard, it has been a grand mystery to experience and appreciate how the answers to my prayers in the NHGC have transformed me into an answered prayer for others.

What are you doing at the NHGC? As the first NHGC Biophysics Research and Interdisciplinary Development Group (BRIDG) Postdoctoral Scholar, I have been charged with developing the science of the quantum nature of genome action and its implications for biology. The field of quantum biology has exploded in the last decade, producing major advances in our understanding of fundamental life processes such as photosynthesis, vision, magnetoreception, smell, and neurocognition. New tools and technologies are emerging that exploit the ultra-efficient energy transport and environmental sensing capabilities afforded by quantum mechanical processes. Researchers in these areas have forced a sea change in our willingness to accept that the strange world of quantum entanglement plays a role in our daily experience of reality. As it was with the major advances in twentieth-century physics— quantum mechanics and relativity— questions of twenty-first-century science have spurred onward questions of epistemology. Quantum biology has driven scientists to reexamine long-held assumptions of origins, purpose, and identity, thus motivating a re-assessment of wisdom received from the ancients. With an unrelenting focus to interrogate unquestioned dogmas, I am inspired by the fresh life that comes from recognizing truth outside of established norms and well-trod paths. The study of quantum coherent energy transport in biomolecules is expanding our understanding of the mechanisms of disease pathogenesis and our vision for therapeutic options. In particular, I am working with colleagues in the Howard University College of Medicine Geriatrics Research Unit and at Nova Southeastern University’s Institute for Neuro-

Immune Medicine to develop better computational models of microtubule network stimulation in older African Americans, in order to discover better ways to slow the progression of Alzheimer’s disease with changes in exercise. I also collaborate with the Association for Medicine and Complexity in Trieste, Italy, on experimental prediagnosis of various cancers with magnetic fields. We want to test the hypothesis that cancer may be detectable as systemic, global phenomena in the body before localization occurs in specific organ systems. In November 2015, an Italian physicist and I published3 the framework we developed for these experiments using quantum field theory, touted as the most accurate scientific theory to date and on which the standard model of particle physics is based. We expect to begin clinical trials in the next year. My work as a biophysicist takes two general forms: 1) the derivation and development of new laws from fundamental theoretical principles, and 2) the translation of these laws into clinical applications for biomedical science. I have mentioned above some of these applications in neurodegeneration and other degenerative illnesses. More specifically, I examine how coherent energy flows in nucleic acid and protein structures mediate communication or maintenance of information across significant biological distances and timescales. This research program forces a shift in our understanding from biochemical processes to biophysical targets, and from pharmaceutical interventions to complementary and alternative energetic treatments. Might there be a scientific basis for ancient practices like tai chi, acupuncture, and the laying on of hands? Certainly, we will not be able to answer this question if we remain closed to the metaphysical possibility that such a relationship exists.

Analysis of biological systems through the lens of physical laws has provided us insight into the role that consciousness plays in health, life, and the universe. DNA appears to be more curious a molecule than we could have expected at the time of Watson and Crick’s discovery, possessing both classical and quantum information storage capacities that emerge from finely tuned structural properties of the double helix. Such quantum information processing may be reflected in multiple levels of a fractal-like hierarchy from the genome to the rest of biology, including in neuronal networks of the brain. This holographic aspect of the genome, where an image of the whole is reflected in each of the parts, may be an intrinsic property of the universe itself. Indeed, physicists have formulated holographic principles for black holes and information processing at the cosmological scale. Heady stuff for sure, but essential to a truer and more whole description of life. This work is leading us to a deeper appreciation of physical reality and the interconnectivity of human experience within it, promising the hope of better treatments for disease and illness. How does your work benefit humankind? What are the challenges? I believe that knowledge, awareness, and application of truth are the surest way to the betterment of human health and the human condition. NHGC scientists work diligently toward developing more accurate models of truth. In these efforts, our goal has always been to more faithfully describe the reality in which human beings find themselves. But in the midst of our questioning and probing, still we recognize that Western science has long been hindered by its penchant to exalt scientific models as the fundamental reality itself. In the domain of biomedical science, the result has been to replace the true complexity of human nature with an overly reductionist

construct. Instead of the truth, we have become complacent with unsatisfying proxies that do not capture its essence. Informed simplification is essential to the art of science. Everything in the infinite hierarchy of knowledge cannot be included in a finite model, and judicious choices must be made about where to cast the intellectual nets. However, scientists become tyrants when we vehemently deny as non-existent that which lies outside or beyond our limited models. Scientists in this spirit have dismissively excluded aspects of nature that emerge from wholistic interactions among the parts.

I am inspired by the fresh life that comes from recognizing truth outside of established norms and well-trod paths.

biomedical models to more fully address the challenges of healing and healthcare. Science is confirming that what we choose to identify with and believe has an impact on our experience of reality and on health and disease. The NHGC BRIDG is at the forefront of addressing these challenges, uncovering truth wherever it may be found for the benefit of all, especially for the least among us. I am blessed and privileged to be a part of this journey. Citations P. Kurian. Quantum entanglement in the genome? The role of quantum effects in catalytic synchronization of type II restriction endonucleases. Ph.D. thesis, Howard University, Washington, DC (2013).

P. Kurian, G. Dunston, and J. Lindesay. How quantum entanglement in DNA synchronizes double-strand breakage by type II restriction endonucleases. Journal of Theoretical Biology, in press (2016).

P. Kurian and C. Verzegnassi. Quantum field theory treatment of magnetic effects on the spin and orbital angular momentum of a free electron. Physics Letters A 380, 394 (2016).

We are humbled by the gift of revelation we have received along the path toward “quantum genomics,”2 which has provided NHGC researchers with glimpses of a scientific view of the soul. Acknowledgment that human beings are more than just body and mind is perhaps the greatest hurdle faced by science in the twenty-first century. Expanding our scientific worldview to include questions of intention, will, purpose, and identity is the challenge before us as we attempt to make sense of the vicious inequalities faced by people of African descent across the globe. How our genomes (body) interact with consciousness (mind) to produce individual choices (spirit) is a central question when considering health disparities and genomeenvironment interactions—the new watchword in the age-old nature vs. nurture debate. Our sense of self— the chorus of inner voices that responds to the question of “who I am”—should be incorporated into

Towards an African view of human genetics Latifa Jackson, PhD My passion for human genetics is braided from three main strands of experiences. The first strand is growing up all over the world, seeing human diversity in its natural state.Â Â From Tanzania to Liberia, Cairo to Copenhagen, I have been fortunate to live and work on four continents. These experiences have concretized the observation that human diversity is a constant both within and between populations. The role of culture and environment in shaping our micro-adaptive processes is compelling. The second strand of experience to becoming a human geneticist came from my love of genetics itself. This is a dynamic field that continues to widen the tent in terms of what forces are contributing to the diverse phenotypes that we observe in humans. When I started to study genetics, the foci of most research projects were Mendelian traits, whose genetics could be ascribed to single gene loci. Today we are looking at much more complicated systems of inheritance including complex multi-locus genetic traits. The third strand is woven from my work in HIV/ AIDS prevention development work. I worked on public health projects in West Africa and saw firsthand the effects of infectious diseases like polio, malaria, and HIV in shaping individual and societal well-being. From that moment onwards I was determined to use genetics to improve health outcomes for people suffering under undue disease burden. I earned my masters in Ecology and Evolutionary Biology from the University of Arizona and my Ph.D. in Biomedical Science from Drexel University. Each of these academic settings provided opportunities to learn cutting-edge research techniques that I have brought to my postdoctoral fellowship. Since joining the National Human Genome Center (NHGC), my work has focused

on projects tied to examining the effects of genome variation on human populations with respect to health disparities. When I first started postdoctoral work at the NHGC, I thought that my path would follow the long progression of work that I had undertaken in molecular labs and public health sites, while starting to learn some computational approaches. Indeed, it has been shaped by these experiences and expertly guided by my postdoctoral advisor, Dr. Georgia Dunston. My work takes an evolutionary perspective, uses a systems biology framework, and implements computational approaches to address questions of health disparities in African Americans. The algorithm that I developed during my dissertation work to look at chronic non-communicable diseases has proven quite tractable in examining infectious disease and the long-term genetic effect of health disparities in African Americans. Now I am working on projects that focus on four main areas. The first is how health disparities have influenced African American population genetics. This means trying to identify variants underlying complex health disparities as a means to improve our understanding of the genetics underlying complex traits. This work is in direct contrast to Mendelian genetics, where misregulation of one gene leads to a disease phenotype. Instead, we have potentially thousands of genes contributing to a phenotype, and we need to develop more sophisticated methods to deal with this reality. One way to do this is to use the lens of functional approaches. We have used this approach to study the effects of hypertension, mental health, and blood-based disorders in African ancestry populations. This work has been presented at national and international health

disparity and meetings.

human

genetics

Another question that we are working on is related to genome structure and organization. This is a really important question as we start to think about variation in human populations. We know that variation is partitioned in human populations and that this variation at the sequence level has functional implications in trait space. Structural variation is also partitioned in human populations. For example, recombination hotspots occur more frequently in individuals of African Ancestry than they do in nonAfricans. We know that there are features of the genome that appear to be very important in inheritance processes. We want to develop an information map based on entropy, a measurement of disorder in the genome. This information map can tell us about the information associated with genomic organization and content. We hope to examine interand intra-individual differences that may be playing a role in variation in human populations. This research will add a critical component to our understanding of how information content, like variation, might be partitioned in human populations. For the past year, the NHGC has had a memorandum of understanding with the W. Montague Cobb Research Lab to collaborate on the study of the genetic basis of health disparities in historical African Americans in the Washington, DC, area. One of the unique aspects of this work is that the Cobb collection is populated with individuals from the Washington, DC, area who lived between 1860 and 1959. This collection allows us to test variants of interest identified through our computational algorithms, to be genotyped in a historical African American population that is unique in its size and provenance. Our work on mental health conditions in the

The role of culture and environment in shaping our microadaptive processes is compelling.

Cobb collection has been accepted for publication in an upcoming issue of the American Journal of Human Biology. As the field of human genetics has progressed, increasing emphasis has been placed on the genetics of African diasporic populations. This makes sense in the context of African contributions to human genomic diversity and to the biomedical struggle to combat health disparities through the prism of personalized medicine, including the initiatives recently announced by President Obama. This work requires a comprehensive strategy to sampling those African populations that contribute to African American populations. Recent efforts from the National Institutes of Health and Wellcome Trust on the Human Health and Heredity (H3) in Africa initiative have sought to better characterize African diversity, which will aid the goal of closing our gaps in understanding African American genomic diversity. Unfortunately, the current opportunistic sampling strategies do not go far enough in assessing variation from those ethnic

populations that historical records tell us contributed most to African diasporic genetic variation. We believe that we can make substantive contributions to this field and have begun to develop models of African sampling strategies to capture a true representation of the genetic diversity inherent in African American populations. I am excited to continue to develop my research projects within the NHGC and under Dr. Dunstonâ&#x20AC;&#x2122;s supervision. I have been grateful for the amount and diversity of research collaborations that occur here at Howard University.

Quantum biology has driven scientists to re-examine long-held assumptions of origins, purpose, and identity. - Philip Kurian, PhD

What Attracted Me to the National Human Genome Center at Howard University? Tshela Mason, MS Molecular Biology What initially attracted me to the NHGC was the mission statement of the Center, which is “to explore the science and teach the knowledge of DNA sequence variation and its interaction with the environment in the causality, treatment, and prevention of diseases common in populations of African descent.” The Center’s commitment to educating underserved communities about the importance of their participation in scientific research appealed to me as well.

Victor Apprey, PhD My academic work involves Operations research, Applied Statistics and computation of large data sets. I was drawn to the field of Genomics because I wanted to develop algorithms for decision-making and “what-if scenarios” in an automated function.

Bradford D. Wilson, PhD My experience at the National Human Genome Center began as a volunteer. I felt honored and privileged to work with distinguished researchers investigating the genetics underlying the biology of conditions and diseases that disproportionately affecting people of color. Health disparities research continues to be of great importance not only to African Americans and people of African descent, but to all of humankind. I am proud to continue this work and be of service to my community.

Ashelyn Q. Mack Several years prior to the founding of the National Human Genome Center in 2001, I was fortunate to have a position in the Department of Microbiology as a research assistant helping families learn about and manage asthma in children. The project’s lasting effect was not forgotten and continues to be distinctly motivating, imprinting the notion that we as a people can “help us, help us.” Little did I know, that project would spark my interest in health disparities among African Americans and people of African descent. The importance of how we can make a difference and be the difference, at Howard University, the “Mecca” for the Black community, could in fact, bridge this gap or, for that matter, be the bridge that brings health equity to the underserved and disenfranchised. Daniel Achinko, PhD What attracted me to the NHGC is the ideology behind the Center’s goal. NHGC researchers take into consideration the contribution of multicultural DNA variation in the human genome, and greater understanding of that variation can be used to promote health and prevent disease. This forms the fundamental basis on which health should be focused in this current generation because the world is a global village. Ethnic diversity and interactions contribute to the observed dynamics of any public health problem. The great learning and research environment offered by the NHGC is targeted towards understanding the complexities within DNA, which will help us to decipher genetic information in different populations and bring new therapeutic approaches to current disease challenges.

Muneer Abbas, PhD The National Human Genome Center provides a rich research environment to study health disparities in people of African ancestry, which has broad implications for better understanding of common complex diseases in all human populations.

Interdisciplinary Research Building - The Howard University Interdisciplinary Research Building (IRB) is a cornerstone of the Universityâ&#x20AC;&#x2122;s academic renewal initiative, and its prominent gateway location on the Georgia Avenue Corridor is a public expression of Howardâ&#x20AC;&#x2122;s commitment to 21st-century research. The IRB was conceived, designed and constructed to foster collaborative interdisciplinary research at the University. The new 81,000 square-foot, mixed-use academic building will support and promote interdisciplinary research and educational collaboration. The research building is designed as an energy-efficient (LEED) facility that incorporates cutting-edge technology and the latest educational, environmental and research standards.

Through the expansion of our interdisciplinary collaborations, we will maximize our strengths as a University. The University becomes much larger than the sum of its parts, and strategically positioned to serve the local, national and global community while fulfilling its mission as a research institution. -President Wayne A.I. Frederick, MD, MBA, FACS 22

Soul The Sole Determinant of Health and Disease Soul Science: A Time for Whole-Genome Transformation of Human Identity Georgia M. Dunston and Philip Kurian “Junk” De-Bunked Three decades prior to the completion of the Human Genome Project (HGP), the term “junk DNA” was formalized in the human genome lexicon to refer to huge swaths of DNA not known to play a functional role in development, physiology, or some other organism-level capacity. In September 2012, the Encyclopedia of DNA Elements (ENCODE) – a public research consortium launched by the National Human Genome Research Institute – released the first tranche of papers assigning biochemical function to 80% of single nucleotide polymorphisms (SNPs) associated in genome-wide association studies (GWAS) with disease phenotypes. This treasure trove of highprofile research papers provided convincing evidence that the genome is pervasively transcribed. Since the vast majority of SNPs identified in GWAS are in nontranslated regions, it is known that the underlying mechanism linking them to the disease phenotype is likely to be regulatory. The ENCODE project has been a massive global research effort to map and characterize the functionality of the three billion nucleotide bases of the complete human genome sequence. By assigning biochemical functionality to the vast majority of the

DNA sequence in non-protein-coding sequences, ENCODE data have challenged earlier thinking on “junk DNA.” In overturning such a shortsighted brand of reductionism, the ENCODE consortium’s work has stimulated a Copernican Revolution in thinking about the functional landscape of human genomics for the twenty-first century. The Perils of Compartmentalizing Human Identity The sequencing of the whole human genome has opened new vistas for interrogating the biology of the whole person. Most epidemiological categorizations and classifications of individuals and population groups use self-identified racial groupings based on perceived biological phenotypes encoded in what is now known to be less than 0.1% of an individual’s whole-genome sequence. The impact on health and disease of DNA sequence variation between individuals, families, and populations in regions of non-protein-coding sequences is an active arena of current research. The ENCODE project highlights that a significant amount of whole-genome biology resides in the interplay of complex systems of non-protein-coding sequences that function in the control and regulation of protein-

coding sequences used in defining most biological phenotypes. Time and again, our misunderstandings of how to define the boundaries of humanity—where “I” or “we” ends and the “other” begins—have led to fear, violence, and oppression. The question that we are revisiting in human genome research today is this: How can we define individuals or human population groups without the use of familiar and ingrained prescriptions, which rely largely on what is seen on the surface at the expense of what can be learned from the whole genome sequence within? Such inquiry has been fraught with difficulty throughout modern science’s attempts to address it, harkening to the darkest days of phrenology and eugenics. The emergence of genomic medicine shifts the focus on external phenotype to the internal genotype, with a change in how we define genes, diagnose disease, and treat patients. In genetic epidemiology, human populations are often defined by the most common alleles or traits in the group. The shift toward personalized/precision medicine poses difficulties in categorizing individuals who do not fit the racial phenotype, thereby rendering the term “race” and racial groupings an anachronism in modern molecular medicine. The advent of affordable, large-scale genome sequencing offers the exciting possibility that we can now incorporate a person’s genotype in our definition and fundamental understanding of human biology, personal identity, and population diversity. The human genome is forcing us to become aware of how we see and define ourselves, which is related to the health of our bodies, the integrity of our communities, and the stability of our world. But, when attempting to scope something as significant as identity, we must be careful to look at the whole genome, and not just cherry-pick genes and other isolated portions that suit our preconceived concepts of human biology. While skin color and anatomical features are

certainly biological in their basis, we have connected “race” to these phenotypic observables and therefore erroneously concluded that race is biologically determined and, as an unfortunate corollary, that race is a biological determinant of health and health disparities. The human genome sequence provides evidence that race is neither a reproducible biological construct for genome-wide association studies (GWAS) nor an authentic measure of biological plausibility in analyses of DNA-sequence-based constructs of human identity. Patently, identity cannot be understood at the level of what is seen on the surface. Yet that is precisely the trap we’ve fallen into—that of using race as a proxy for a biosocial construct. Race is, fundamentally, an inappropriate basis for defining human identity. When one asks the question of human identity, the basis must be the whole person, all of what is inherited in the genome, including the whole genome’s interactions with the environment. To deal with common diseases—public health problems such as obesity, hypertension, diabetes, asthma, and cancer that affect large numbers in all populations, and where multiple genes are involved that do not follow the laws of classical Mendelian inheritance—we must correct for how we define ourselves on the basis of only a limited portion of our total inheritance. We must take into consideration the

whole human genome and now ask, indeed demand, to define ourselves using knowledge gained from a whole-genome consciousness of our biological inheritance. The Soul Consciousness in Human Genome Variation Research The late Francis Crick, co-discoverer of the DNA double helix with James Watson and Rosalind Franklin, published a book in 1994 entitled The Astonishing Hypothesis: The Scientific Search for the Soul. In it, Crick made bold strides toward dispelling the scientific community’s reluctance to engage issues of human consciousness, identity, and purpose. In those pages, he further encouraged engagement between philosophers and neuroscientists to explore questions of free will and, ultimately, the constitution of the soul. Now in 2015, two decades since the publication of Crick’s book and one decade since his passing and the completion of the HGP, it is now time to reassess information on the science of the soul revealed in sequencing the whole human genome. We find it intriguing that our explorations of the human genome and the mysteries of life encoded in DNA, like Crick’s search for the soul, have led to a deeper appreciation of science’s most compelling unknowns and its limitless possibilities to create dialogue with, and even inform, the most ancient of spiritual truths.

Race is, fundamentally, an inappropriate basis for defining human identity.

Indeed, the scientific mission of the NHGC at Howard University is motivated by knowledge gained from the HGP and human genome variation that enables us to understand more intimately and completely who we are as individuals, and as populations of African ancestry separated by the expanse of oceans between the Old and New Worlds. Such is the depth of our genomic connection, from which we can glean novel insights on our shared biology and common identity encoded in the exquisite diversity of the human genome family. Of course, the scientific and the spiritual have not always made amiable bedfellows. Great thinkers throughout the ages have wondered about the soul. Questions abound: What is it made of and what contains it? Are human souls unique? Where do they come from? How do they interact with the natural world? Thomas Aquinas in his Summa Theologica attributed the soul to all organisms but espoused the belief that immortal souls capable of union with the divine belong only to human beings. Animistic faiths and religions like Hinduism shared Aquinas’s conviction that all living things have souls, while others considered natural objects such as rivers and mountains to possess souls.

foundation for defining human biology and identity, the secrets of genomic life are now revealed through decoding the structure of whole-genome sequence variation. What is unseen, and thus invisible to our previous genetic paradigm, has now claimed its rightful place as the predominant component of our biological inheritance. From the human genome perspective, life extends across all generations, and yet is personalized in each member of humanity. The whole genome is our common inheritance, individually and collectively. Such can be the biomedical scientist’s view of the soul, as each unique expression of life expressed through the biology of whole-genome identity. Thus, one of the lessons learned from the HGP and research on human genome variation is that human identity is the expression of one incredibly whole Life consciousness. Overwhelming data from the HGP and research on human genome variation in populations show that more than 99% of the complete DNA sequence from any two persons randomly selected from any two places on the globe is essentially the same. If information encoded in DNA sequence variation reveals humankind as one interrelated, extremely diverse, and inextricably whole human family, then it follows that the genome is programmed and purposed from the birth of each person to express and experience whole-genome life. And perhaps, we may find a new beginning for the human family in our awareness of and identification with this abundant Life—a profound sense that we are more than just the sum of parts. Indeed, we are each essential components to the synchronous workings of the Whole.

This article is excerpted from a longer paper published in Italian in the 2014 Conference Proceedings of “Physics Interacts with Medicine, Art, and Spirituality” (Associazione Medicina e Complessità, Trieste, Italy).

The Greek philosophers of the Socratic tradition believed the soul to be the center of the human faculties of reason, emotion, and desire. Plato popularized the notion of the Anima mundi, or “world soul,” which describes the intrinsic connection between all living things, writing that “this world is indeed a living being endowed with a soul and intelligence... a single visible living entity containing all other living entities, which by their nature are all related.” Aristotle viewed the essential purpose of a living thing—its joie de vivre—as the soul. As the whole cannot be understood fully by a single part, so the whole genome cannot be understood by a subset of genes that comprise it. Mysteries underlying the organization and expression of life in and through the whole genome are waiting to be discovered, as treasures hidden deep within the nuclei of the trillions of cells making up the human body. In the fullness of time, with whole-genome sequencing as a new

Niya McKie

THE 2 ND DECADE N EX G EN G ENOMICS